Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR As Opposed to Sporadic Burkitt Lymphoma

Overview

Journal Am J Clin Pathol

Publisher Oxford University Press

Specialty Pathology

Date 2015 Dec 30

PMID 26712879

Citations 22

Authors

Teresa Amato

Francesco Abate

Pierpaolo Piccaluga

Michele Iacono

Chiara Fallerini

Alessandra Renieri

Giulia De Falco

Maria Raffaella Ambrosio

Vaselious Mourmouras

Martin Ogwang

Valeria Calbi

Roul Rabadan

Michael Hummel

Stefano Pileri

Lorenzo Leoncini

Cristiana Bellan

Affiliations

Soon will be listed here.

Abstract

Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma.

Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs).

Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL.

Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.

Citing Articles

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